National Institute of Allergy and Infectious Diseases (NIAID)
National Cancer Institute (NCI)Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD)
National Institute of Mental Health (NIMH)
National Institute on Drug Abuse (NIDA)

May 30, 2013 (NOT-OD-13-074) -
NIH to Require Use of Updated Electronic Application Forms for Due Dates on or after September 25, 2013. Forms-C applications are required for due dates on or after September 25, 2013.

This Funding Opportunity Announcement (FOA) invites
applications addressing ethical issues in research relevant to populations
with HIV and associated co-morbidities, and populations at high risk of HIV
acquisition. The bioethics projects supported through this program
announcement will focus on at least one of the following three goals:

1) Development of the empirical knowledge base for human
subjects protection and ethics standards in HIV/AIDS research;

2) Development of conceptual bioethics approaches to
advance scholarship on difficult ethical challenges in HIV/AIDS research;

3) Supporting the integration of bioethics work with
ongoing research in HIV/AIDS.

Key Dates

Posted Date

July 24, 2012

Open Date (Earliest Submission Date)

November 7, 2012

Letter of Intent Due Date

Not Applicable.

Application Due Date(s)

January 7, 2013; January 7, 2014; January 7, 2015, by 5:00 PM local time of applicant organization.

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

February-March, 2013, February-March, 2014; February-March,
2015

Advisory Council Review

May, 2013; May, 2014; May, 2015

Earliest Start Date(s)

July, 2013; July, 2014; July, 2015

Expiration Date

January 8, 2015

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide, except where instructed to do otherwise
(in this FOA or in a Notice from the NIH Guide for Grants and
Contracts). Conformance to all requirements (both in the
Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

Applications for support under this FOA may include
conceptual work in bioethics, or empirical work gathering and analyzing data
relevant to ethical issues in research, or a combination of the two. For
empirical projects, data collection may include quantitative or qualitative
methods, or both.

For all applications, the research team is strongly
encouraged to include at least one person with demonstrated expertise and
scholarship in bioethics, as demonstrated by academic work and publications in
the field.

For projects involving empirical data collection,
applicants should describe how the data collection will inform current or
future ethical deliberations or ethical oversight processes; the research team
should include at least one social scientist or other researcher with relevant
expertise in theory and methodology for conducting the proposed empirical
research.

For projects which are purely conceptual or analytical
bioethics work and do not involve empirical investigation, applicants should
describe: the current state of scholarship on the topic; why the proposed
project is significant and innovative, for example, whether new reasoning is
applied to a familiar problem, or whether a new problem is addressed; and what
type of theoretical framework or approach will be used to address the problem.

For projects which combine conceptual work in bioethics
with empirical data collection, applicants should describe how the data
collection informs ethical analysis or decision making, in addition to
addressing the requirements for conceptual work as stated above.

Applications addressing empirical research on informed
consent will not be funded under this Program Announcement, with the exception
of informed consent/assent/parental permission related to adolescents as
research participants, as described below. For other funding opportunities
related to informed consent, please see PA-11-180, PA-11-181,
and PA-11-182.

The following selected bioethics topics are of particular
interest; however, other ethical issues are relevant and this list is not
intended to be exhaustive.

Ethical Issues
in Research Utilizing Human Specimens

Research utilizing specimens is vital to progress in
biomedical science and public health. Although research utilizing specimens is
usually classified as minimal risk, international collaborative research
involving specimens can involve ethical, legal and political complexities that
sometimes stymie important projects. For example, the burden of oversight and
regulation of research with specimens may seem disproportionate to the level of
risk. There are divergent views amongst stakeholders about how research utilizing
specimens should be regulated, whose interests are at stake, and how these
interests ought to be protected. A variety of other issues have been raised by
stakeholders, including perceptions and misconceptions about likelihood of
breaches of confidentiality, worries about the acceptability of research with
banked specimens, concern about potential impact of research findings on
communities, and issues regarding control of specimens in multi-national
research collaborations.

Possible topics include, but are not limited to, the
following:

Empirical assessments and ethical analysis of documented harms
and benefits associated with specimen research, including effects on
individuals, communities, clinical practice, public health and science;

Development of interventions to address misconceptions or lack of
information about HIV-related research with specimens, amongst the general
public, communities and individuals at risk of or affected by HIV, ethics
committees and IRBs, both in the US and in other countries;

Development of models of shared decision-making and governance
for use of specimens in international collaborative research, with particular
focus on developing countries.

Ethics of Research
Involving Pregnant Women

The care and treatment of pregnant women in the US and
around the world is hampered by a lack of rigorous clinical trial evidence to
support treatment choices. The vast majority of interventions needed by these
millions of women are either used without specific evidence of efficacy or
safety during pregnancy, or avoided due to concerns about effects on fetal
health. As a result, pregnant women and their offspring often suffer from
suboptimal health care. Research involving pregnant women is often limited by
the difficulty of adjudicating risks and benefits to mother and fetus, and the
challenges of obtaining associated regulatory approvals. In HIV research, the
early advent of antiretrovirals for prevention of mother to child HIV
transmission has resulted in a substantial evidence base for use of these drugs
during pregnancy. However, significant gaps remain. More research is needed
on treatment of HIV-infected pregnant women for indications other than
prevention of maternal to child transmission. Serious co-morbidities such as tuberculosis
(TB) are often under-treated in pregnant women, and research to extend new
treatment modalities for this population remains ethically challenging.
HIV-uninfected pregnant women urgently need HIV prevention agents that have
been proven safe and effective, especially since there are data showing
significant, perhaps even heightened, risk of HIV acquisition during
pregnancy.

Projects which help advance the ethical agenda for research
with pregnant women could include, but are not limited to, the following:

Gathering and analyzing information from stakeholders (patients,
clinicians, researchers, ethics committees/IRBs, regulators) about ethical
priorities and challenges in research with pregnant women, including
comparative ethical analysis of research with pregnant women in other disease areas;

Projects to gather and analyze biomedical data related to
pregnancy and create a scientific and ethical framework for analyzing risks and
benefits of research with pregnant women;

Analysis of ethical and regulatory oversight of research with
pregnant women, in the US or in other countries; development of policy
strategies for improving the research agenda for pregnant women.

Ethics of Research
Involving Adolescents and Young Adults

Care and treatment efforts for HIV-infected adolescents and
young adults in the US and around the world, as well as prevention efforts for
those at risk of infection are compromised by a lack of rigorous clinical trial
evidence to support management approaches and treatment choices. A vast
proportion of biomedical interventions and therapies used in these populations
are implemented in the absence of specific data to support indications for
their use and are often justified by extrapolation from studies in much older
adult populations. Substantial biomedical and psychosocial data suggest that
adolescents are simply not smaller adults and that such dogmatic approaches
result in less than optimal care.

Investigators frequently encounter a variety of difficulties
in working with youth which create a disincentive to carry out research in
these populations, such as individual factors (non-adherence, risk behaviors
and other psychosocial challenges) and structural barriers (ethical, legal and
regulatory issues). There have been important milestones achieved in HIV
prevention and treatment; however, concerns about adherence problems in youth
are barriers to their implementation in this group. There is an urgent need for
primary and secondary prevention among youth populations who are at high risk
of acquisition or transmission of HIV, both globally and domestically. An
adolescent’s evolving autonomy, decisional capacity and individuality argues
for a right to independence and self-determination when it comes to their
health care. However, there are ethical, legal and regulatory considerations
that vary by jurisdiction and geography which impact these rights and create
obstacles to research and health care. Projects to address issues related to
adolescents in research could include, but are not limited to, the following:

Conceptual and empirical work on issues of evolving adolescent
autonomy, decisional capacity, consent, assent and parental permission,
particularly in regard to youth at risk for HIV infection and other STDs in the
US and in other countries;

Analysis of legal provisions for protection of confidentiality of
minors and for rights to self-determination and decision-making by adolescents
about participation in research; analysis of these legal and ethical issues in
various research settings. Relevant research contexts include research on mood
disorders, sexual behaviors, and substance use, as well as other potential risk
determinants for HIV acquisition, such as homelessness, incarceration, truancy,
and other circumstances and conditions;

Projects to gather and analyze biomedical, behavioral and other
psychosocial data related to adolescents and young adults to create a
scientific and ethical framework for analyzing risks and benefits of research
with youth; legal and ethical analysis of minimal risk standard for research as
applied to adolescents.

Ethical Issues
in Research on an HIV Cure

A new area in HIV research is the search for a means to
eradicate the virus from the body—an HIV “cure.” While effective
antiretroviral treatment has been hugely successful in reducing morbidity and
mortality from HIV infection, the virus is never wholly eliminated from the
body and patients must remain on lifelong treatment. The goal of cure research
is to determine where and how the virus lies dormant and develop treatment
algorithms that stimulate and eliminate virus reservoirs. A significant
ethical challenge with this area of research is that early phase and
translational trials will need to be conducted with relatively healthy HIV-infected
patients. Specifically, risks and benefits of this type of research are
difficult to assess, and patients may develop misconceptions about the
likelihood of success. Projects addressing these issues could include the
following:

Analysis of risks and benefits of HIV cure research to
individuals and future patients, including social value of research for
developing future biomedical interventions;

Learning from and applying ethical frameworks from early phase
research in other disease areas; conducting comparative ethical analysis of
early phase research in different settings.

Standards of Care
and the Interaction of Statistics and Ethics in Clinical Trial Design

Ethical dilemmas in the choice of standard of care or
prevention in clinical trials have been deep and enduring. Key considerations
in clinical trials, such as the need to provide adequate benefit to trial
participants, the need for research to be socially valuable and useful, the
need for rigorous design that enables sound scientific inferences, and the need
for efficiency, often result in difficult tradeoffs in trial design. Trial
designs that maximize one important aspect may, to some extent, sacrifice
others. Discussions of optimum design must include stakeholders with expertise
in statistics, clinical medicine, health policy, and ethics. Interdisciplinary
projects addressing standards of care or prevention could include the
following:

Ethical and scientific analysis of current clinical trial design
approaches to address changing standards of care in HIV prevention and
treatment;

Conceptual research in bioethics addressing stakeholder
obligations in standard of care dilemmas in HIV-related research;

Analysis of ethical and scientific advantages and disadvantages
of innovative statistical methods and trial designs to HIV related research to
address changing standards of care; methods for predicting value of different
trial designs for decision making in clinical care and health policy; ethical
and policy analysis of social value of different trial designs.

Effectiveness
of Research Ethics Committee Review

The process of research ethics oversight by ethics
committees and IRBs, a critical part of the ethical conduct of research, by
necessity creates some burden on the research enterprise. It is essential to
ensure that these review processes are effective and efficient. Multi-center
clinical trials and international collaborative research projects pose
particular challenges for ethics/IRB review. Some approaches include, but are
not limited to, the following:

Development of tools for the measurement of the effectiveness of
ethics committees/IRB deliberations and substantive decision-making (as
distinct from adherence to bureaucratic procedures), both in the US and in
other countries;

Development of models for coordination and communication between
and among IRBs and ethics committees, including shared or collaborative review
processes, where appropriate, with particular focus on international
collaborative research;

Programs to assess challenges, opinions and expectations of research
ethics committees in international HIV/AIDS-related research and to develop
tools to strengthen capacity and improve performance.

Ethical Issues
in HIV Research Using New Forms of Technology

New technological developments or adoption of technologies
in the research setting may raise ethical concerns relating to protection of
research participants and their communities. For example, privacy and
confidentiality concerns may arise in the context of internet research such as online
recruitment or data collection. Use of technologies such as mobile
communication devices and home testing kits could raise issues about
communication of health information and complexities of family and partner
relationships in the context of testing and disclosure. Worries about privacy
and confidentiality may be particularly acute in HIV related research due to
continued stigma and risk of social harms from disclosure of actual or presumed
HIV status. Other new technologies, including biomedical technology as well as
electronic tools, may pose new challenges for the ethical conduct of research.
Projects to assess ethical issues arising in use of new technologies could
include, but are not limited to, the following:

Empirical assessments and ethical analysis of documented harms
and benefits associated with the use of new forms of technology in HIV
research, including effects on individuals, communities, clinical practice,
public health and science;

Development of best practices for minimizing risks, monitoring
adverse events and social harms, or addressing these consequences as they arise
when data are collected remotely using internet, mobile devices or other
technology;

Research to determine best practices for ethics committees and
IRBs, both in the US and in other countries, when providing oversight of
research using newer forms of technology.

Research in Settings
of Stigma, Discrimination and Oppression

There is widespread stigma, discrimination and oppression
directed at men who have sex with men (MSM), sex workers, and intravenous drug
users (IDU) throughout the world, which, beyond direct adverse effects on these
groups, hampers HIV prevention, care and treatment efforts. For these groups,
criminal sanctions exist in many countries and both the threat and reality of
incarceration are widespread. Women and girls at risk for, or experiencing,
violence or sexual abuse are at increased risk of HIV acquisition, and may face
additional barriers in accessing appropriate care. In addition to these conditions,
disclosure of HIV status continues to be a major challenge for people living
with HIV around the world. Access to care and treatment, social support,
coping, and prevention of transmission of HIV to others are all adversely
affected by difficulties with HIV disclosure.

Projects addressing these issues could include, but are not
limited to, the following:

Ethical analysis of potential obligations of stakeholders,
including researchers and research sponsors, to address background conditions in
the context of research studies with oppressed groups; development and
assessment of training tools for investigators and research staff to promote
appropriate and ethical conduct of research with vulnerable populations;

Analysis of risks and benefits of conducting research in these
settings; determining ethical approaches to conducting research while
minimizing risks of further harms; assessment of potential for research to contribute
to, exacerbate, or alleviate inadvertent disclosure or stigma;

Gathering and analyzing information from stakeholders (patients,
clinicians, researchers, ethics committees/IRBs, regulators) about ethical
priorities and challenges in research with individuals living with HIV, or at
high risk of HIV infection, facing stigma, discrimination, legal sanctions
and/or interpersonal violence;

Use of rapid policy assessment and other analytic approaches to
evaluate legal, economic or political barriers to research in settings of
stigma or oppression; developing ethical and policy frameworks to appropriately
guide research in difficult political contexts.

Ethical Issues
in Research Related to HIV and Tuberculosis (TB)

Research and public health programs on TB raise multiple ethical
issues, due to the characteristics of the disease and its clinical management.
These characteristics include the transmissibility of TB, difficulties in TB
diagnosis, challenges of TB treatment and follow-up, and the rise of multiple
drug resistant (MDR) or extensively drug resistant (XDR) TB. TB in the context
of HIV infection is more challenging to prevent, diagnose, and treat, as is TB
infection in children; research and clinical practice in these groups raise
more difficult issues related to risks and benefits of research and
effectiveness of public health policies. Ethical issues related to TB to be
addressed could include, but are not limited to, the following:

Analysis of ethical challenges of research on diagnostic tests;
should tests that are not fully validated or approved by regulatory authorities
be used to inform clinical care, and if so, what parameters should affect these
decisions? How should risks and benefits of use of new diagnostic tests, both
for patients and others in the community, be evaluated and communicated?

Analysis of ethical issues in introducing new TB drugs: how can
the need for potential benefits of new drugs be balanced with necessary caution
in avoiding development of drug resistance, at the level of individual patient
care, TB programs, and policies? How do these competing obligations influence
the conduct of research and transitions from research to clinical practice,
including the challenges of determining when new agents should be used outside
a clinical trial setting, especially when not all uses or combinations have been
tested in trials; what are the additional challenges of implementing
compassionate use or expanded access programs?

Ethical analysis of risks, benefits and social value of research
on new TB regimens, especially in cases where individual patient benefit is
unlikely or highly uncertain. Examples include studies of new drug regimens in
patients with TB strains already resistant to one or more components of the
regimen being tested; or studies of latent TB, where new agents may be studied
in TB-infected patients who are otherwise healthy, to ascertain anti-latent TB
effects;

Ethical issues arising in drug development and regulatory
approval pathways for new TB drugs, including challenges of testing and
approving combination regimens from multiple companies, and difficulties
reconciling commercial and public health concerns;

Challenges of TB vaccine testing; determining what groups or
populations should be included in TB vaccine studies when individual and
population benefit may vary, and how potential risks and benefits to
individuals and populations can be evaluated and balanced;

Ethical issues in pediatric TB research, including questions of
when new drugs or agents should be studied in children and what kind of
information must be available from adult research or treatment programs to
inform these decisions. When there is uncertainty about TB or MDR TB diagnosis
in children, what is the appropriate threshold for inclusion in TB research
studies? How might potential risks, benefits and social value of research be
evaluated in the context of these uncertainties? When can children be
ethically enrolled in non-beneficial TB research? How can risks and benefits
of TB research and treatment in children be evaluated in the context of
treatment for HIV, where drug interactions may compromise the effectiveness of
one or more treatment regimens?

Ethical issues concerning end of life care for patients with TB.
How can resource allocation, training and decision making for end of life care
be addressed? These ethical challenges may be especially acute in settings
where resources are constrained, and where it may be difficult to determine
when patients are untreatable.

Research on Community
Engagement: Principles and Practices

Community engagement has been a mainstay of research in the
HIV/AIDS arena. However, continuing challenges exist in implementing effective
strategies for community engagement while keeping up with the rapid pace of
research and changes in technology and public health practice. Community Advisory
Boards (CABs) have served a critical function in providing input to researchers
and sponsors about community perspectives on research, yet community engagement
efforts need to be broader and more diverse to effectively address the multiple
challenges of education, communication and dialogue about complex research and
public health issues. Projects to address community engagement could include,
but are not limited to the following:

Assessment of community perceptions and understanding of research
programs; including disagreements or conflicts within communities around
research or public health issues, if any; developing interventions to improve
communication and understanding at the community level;

Assessment of the role of community engagement existing strategies
and interventions in collaborative research including rationale, experience,
effectiveness and lessons learned; assessing benefits and burdens of community
engagement;

Designing and evaluating new community engagement interventions;
developing strategies to ensure that minority voices or views in communities
are heard, or strategies to activate community representation in settings where
no representative structures exist; and exploration of CAB alternatives;

Developing tools and strategies for measuring benefits and
burdens of research at the community level; ethical analysis of appropriateness
of benefits of burdens in different kinds of community settings;

Developing and testing mechanisms for carrying out community
based participatory research (CBPR).

Section II. Award Information

Funding Instrument

Grant

Application Types Allowed

New
Resubmission

The OER
Glossary and the SF 424 (R&R) Application Guide provide details on
these application types.

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH
appropriations, and the submission of a sufficient number of meritorious
applications.

Award Budget

The combined budget for direct costs for the two year
project period may not exceed $275,000. No more than $200,000 may be
requested in any single year. Applicants may request direct costs in $25,000
modules, up to the total direct costs limitation of $275,000 for the combined
two-year award period.

Award Project Period

Scope of the proposed project should determine the project
period. The maximum period is 2 years.

NIH grants policies as
described in the NIH
Grants Policy Statement will apply
to the applications submitted and awards made in response to this FOA.

Section III. Eligibility
Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

Public/State Controlled Institutions of Higher Education

Private Institutions of Higher Education

The following types of Higher Education Institutions
are always encouraged to apply for NIH support as Public or Private
Institutions of Higher Education:

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal
Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

Applicant organizations may submit more than one application,
provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission
Applications from the SF 424 (R&R) Application Guide.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies(GWAS)) as provided in the SF424
(R&R) Application Guide.

Appendix

Do not use the Appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R) Application
Guide.

Foreign Institutions

Foreign (non-US) institutions must follow policies described
in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the SF
424(R&R) Application Package. Failure to register in the Commons and
to include a valid PD/PI Commons ID in the credential field will prevent the
successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for
completeness by the Center for Scientific Review, NIH. Applications that are
incomplete will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

For this particular announcement,
note the following:

The R21 exploratory/developmental grant supports
investigation of novel scientific ideas or new model systems, tools, or
technologies that have the potential for significant impact on biomedical or
biobehavioral research. An R21 grant application need not have extensive
background material or preliminary information. Accordingly, reviewers will
focus their evaluation on the conceptual framework, the level of innovation,
and the potential to significantly advance our knowledge or understanding.
Appropriate justification for the proposed work can be provided through
literature citations, data from other sources, or, when available, from
investigator-generated data. Preliminary data are not required for R21
applications; however, they may be included if available.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following review criteria and additional review criteria
(as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the
strategy establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and injury
to that which is unavoidable in the conduct of scientifically sound research
including the use of analgesic, anesthetic, and tranquilizing drugs and/or
comfortable restraining devices; and 5) methods of euthanasia and reason for
selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the
application as now presented, taking into consideration the responses to
comments from the previous scientific review group and changes made to the
project.

Renewals

Not Applicable.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact/priority
score.

Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications
will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second
level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH Grants
Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH
Grants Policy Statementfor additional information on this
reporting requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.